Addition of metformin to non‐small‐cell lung cancer patients with or without diabetes
Abstract
To the Editor, We read with interest the recently published article by Yang et al. investigating patients with metastatic non-smallcell lung cancer (NSCLC) treated with immune checkpoint inhibitors. The authors concluded that patients with diabetes concurrently taking metformin or a combination of metformin and dipeptidyl peptidase-4 inhibitors had a significantly higher objective response rate (ORR) and progression-free survival (PFS) compared to those without diabetes. We still have some concerns about this article. Metformin, an antidiabetic agent, is proposed to suppress the tumor growth through inhibition of complex I of the mitochondria oxidative phosphorylation chain, activation of AMP-activated protein kinase, suppression of the insulin-like growth factor-I receptor and PI3K/AKT/mTOR pathways, and stimulation of the immune system. It is the first-line agent for most patients with diabetes, but Yang et al. did not evaluate the diabetes complications, comorbidities or report the status of diabetic control in their study. Yang and colleagues also excluded those patients taking other oral hypoglycemic agents or insulin use, which might have eliminated more complicated patients with diabetes. Those patients who take metformin might have been free of more severe clinical conditions such as hepatic impairment, heart failure or chronic kidney disease which are common contraindications to metformin use, and it is not clear whether patients with diabetes in lesser…
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Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design.
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